Hepatoprotective role of α-Lipoic acid and Thymoquinone in Acetaminophen- Induced liver injury

Down-Regulation of COX-2 and flt-1 expression

Nawal M. Al-Rasheed, Laila Fadda, Nouf M. Al-Rasheed, Iman H. Hasan, Hanaa M. Ali, Musaed Al-Fayez, Raeesa A. Mohamad

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1 Citation (Scopus)

Abstract

Acetaminophen (APAP) is a widely-used analgesic, while toxic doses of which induce liver injury. Inducible cyclooxygenase-2 (COX-2) is derived prostaglandins which play an anti-inflammatory role in acetaminophen-induced hepatotoxicity. Selective activation of vascular endothelial growth factor (VEGFR1, flt -1) on endothelial cells increased mRNA levels of hepatocyte mitogens (IL-6) and hepatocyte growth factor leading to prosurvival effects on hepatocytes. The aim of this study was to compare the hepatoprotective effect of N-acetylcysteine (NAC; the antidote for APAP) with that of α-Lipoic acid (ALA) and/or Thymoquinone (THQ) either alone or in combination on liver injury induced by APAP. APAP administration elevated most of the previously measured parameters and decreased GSH, SOD, and total protein levels compared with the control group. Liver sections of H & E demonstrate liver injury characterized by centrilobular hepatocellular necrosis, COX-2, and flt-1 expressions were also increased. Treatment with all fore mentioned antioxidants ameliorated most of the altered parameters compared to APAP-treated group. Treatment with the combination of ALA and THQ was the most effective therapy in the attenuation of liver injury assessed by a decrease in ALT and ALP activities and down-regulation of COX-2 and flt-1 expression. Section of liver from rat received APAP, ALA and THQ shows a marked improvement of hepatic degeneration which restricted to few hepatocytes with mild vacuolation of their cytoplasm while the nuclei appear normal mimic to control cells. It was concluded that the natural antioxidants such as ALA and THQ, may be considered as a potential antidote in combating liver injury induced by APAP.

Original languageEnglish
Article numbere17160703
JournalBrazilian Archives of Biology and Technology
Volume60
DOIs
Publication statusPublished - 1 Jan 2017

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Thioctic Acid
Cyclooxygenase 2
Acetaminophen
Down-Regulation
Liver
Wounds and Injuries
Hepatocytes
Antidotes
Antioxidants
thymoquinone
Hepatocyte Growth Factor
Poisons
Acetylcysteine
Mitogens
Vascular Endothelial Growth Factor A
Prostaglandins
Analgesics
Interleukin-6
Cytoplasm
Anti-Inflammatory Agents

Keywords

  • A-Lipoic acid
  • Acetaminophen
  • Cyclooxygenase-2
  • Thymoquinone

Cite this

@article{ca5c5f0f0ffe420fb23474bf76d84547,
title = "Hepatoprotective role of α-Lipoic acid and Thymoquinone in Acetaminophen- Induced liver injury: Down-Regulation of COX-2 and flt-1 expression",
abstract = "Acetaminophen (APAP) is a widely-used analgesic, while toxic doses of which induce liver injury. Inducible cyclooxygenase-2 (COX-2) is derived prostaglandins which play an anti-inflammatory role in acetaminophen-induced hepatotoxicity. Selective activation of vascular endothelial growth factor (VEGFR1, flt -1) on endothelial cells increased mRNA levels of hepatocyte mitogens (IL-6) and hepatocyte growth factor leading to prosurvival effects on hepatocytes. The aim of this study was to compare the hepatoprotective effect of N-acetylcysteine (NAC; the antidote for APAP) with that of α-Lipoic acid (ALA) and/or Thymoquinone (THQ) either alone or in combination on liver injury induced by APAP. APAP administration elevated most of the previously measured parameters and decreased GSH, SOD, and total protein levels compared with the control group. Liver sections of H & E demonstrate liver injury characterized by centrilobular hepatocellular necrosis, COX-2, and flt-1 expressions were also increased. Treatment with all fore mentioned antioxidants ameliorated most of the altered parameters compared to APAP-treated group. Treatment with the combination of ALA and THQ was the most effective therapy in the attenuation of liver injury assessed by a decrease in ALT and ALP activities and down-regulation of COX-2 and flt-1 expression. Section of liver from rat received APAP, ALA and THQ shows a marked improvement of hepatic degeneration which restricted to few hepatocytes with mild vacuolation of their cytoplasm while the nuclei appear normal mimic to control cells. It was concluded that the natural antioxidants such as ALA and THQ, may be considered as a potential antidote in combating liver injury induced by APAP.",
keywords = "A-Lipoic acid, Acetaminophen, Cyclooxygenase-2, Thymoquinone",
author = "Al-Rasheed, {Nawal M.} and Laila Fadda and Al-Rasheed, {Nouf M.} and Hasan, {Iman H.} and Ali, {Hanaa M.} and Musaed Al-Fayez and Mohamad, {Raeesa A.}",
year = "2017",
month = "1",
day = "1",
doi = "10.190/1678-4324-2017160703",
language = "English",
volume = "60",
journal = "Brazilian Archives of Biology and Technology",
issn = "1516-8913",
publisher = "Instituto de Tecnologia do Parana",

}

Hepatoprotective role of α-Lipoic acid and Thymoquinone in Acetaminophen- Induced liver injury : Down-Regulation of COX-2 and flt-1 expression. / Al-Rasheed, Nawal M.; Fadda, Laila; Al-Rasheed, Nouf M.; Hasan, Iman H.; Ali, Hanaa M.; Al-Fayez, Musaed; Mohamad, Raeesa A.

In: Brazilian Archives of Biology and Technology, Vol. 60, e17160703, 01.01.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Hepatoprotective role of α-Lipoic acid and Thymoquinone in Acetaminophen- Induced liver injury

T2 - Down-Regulation of COX-2 and flt-1 expression

AU - Al-Rasheed, Nawal M.

AU - Fadda, Laila

AU - Al-Rasheed, Nouf M.

AU - Hasan, Iman H.

AU - Ali, Hanaa M.

AU - Al-Fayez, Musaed

AU - Mohamad, Raeesa A.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Acetaminophen (APAP) is a widely-used analgesic, while toxic doses of which induce liver injury. Inducible cyclooxygenase-2 (COX-2) is derived prostaglandins which play an anti-inflammatory role in acetaminophen-induced hepatotoxicity. Selective activation of vascular endothelial growth factor (VEGFR1, flt -1) on endothelial cells increased mRNA levels of hepatocyte mitogens (IL-6) and hepatocyte growth factor leading to prosurvival effects on hepatocytes. The aim of this study was to compare the hepatoprotective effect of N-acetylcysteine (NAC; the antidote for APAP) with that of α-Lipoic acid (ALA) and/or Thymoquinone (THQ) either alone or in combination on liver injury induced by APAP. APAP administration elevated most of the previously measured parameters and decreased GSH, SOD, and total protein levels compared with the control group. Liver sections of H & E demonstrate liver injury characterized by centrilobular hepatocellular necrosis, COX-2, and flt-1 expressions were also increased. Treatment with all fore mentioned antioxidants ameliorated most of the altered parameters compared to APAP-treated group. Treatment with the combination of ALA and THQ was the most effective therapy in the attenuation of liver injury assessed by a decrease in ALT and ALP activities and down-regulation of COX-2 and flt-1 expression. Section of liver from rat received APAP, ALA and THQ shows a marked improvement of hepatic degeneration which restricted to few hepatocytes with mild vacuolation of their cytoplasm while the nuclei appear normal mimic to control cells. It was concluded that the natural antioxidants such as ALA and THQ, may be considered as a potential antidote in combating liver injury induced by APAP.

AB - Acetaminophen (APAP) is a widely-used analgesic, while toxic doses of which induce liver injury. Inducible cyclooxygenase-2 (COX-2) is derived prostaglandins which play an anti-inflammatory role in acetaminophen-induced hepatotoxicity. Selective activation of vascular endothelial growth factor (VEGFR1, flt -1) on endothelial cells increased mRNA levels of hepatocyte mitogens (IL-6) and hepatocyte growth factor leading to prosurvival effects on hepatocytes. The aim of this study was to compare the hepatoprotective effect of N-acetylcysteine (NAC; the antidote for APAP) with that of α-Lipoic acid (ALA) and/or Thymoquinone (THQ) either alone or in combination on liver injury induced by APAP. APAP administration elevated most of the previously measured parameters and decreased GSH, SOD, and total protein levels compared with the control group. Liver sections of H & E demonstrate liver injury characterized by centrilobular hepatocellular necrosis, COX-2, and flt-1 expressions were also increased. Treatment with all fore mentioned antioxidants ameliorated most of the altered parameters compared to APAP-treated group. Treatment with the combination of ALA and THQ was the most effective therapy in the attenuation of liver injury assessed by a decrease in ALT and ALP activities and down-regulation of COX-2 and flt-1 expression. Section of liver from rat received APAP, ALA and THQ shows a marked improvement of hepatic degeneration which restricted to few hepatocytes with mild vacuolation of their cytoplasm while the nuclei appear normal mimic to control cells. It was concluded that the natural antioxidants such as ALA and THQ, may be considered as a potential antidote in combating liver injury induced by APAP.

KW - A-Lipoic acid

KW - Acetaminophen

KW - Cyclooxygenase-2

KW - Thymoquinone

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DO - 10.190/1678-4324-2017160703

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SN - 1516-8913

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